Somatic Cell Hybrids derived by fusion of either mouse or hamster cells with human cell lines were infected with baboon endogenous type C virus (BEV) and scored for virus production. The human and rodent chromosomal content of hybrid cells was identified using assays for 30 gene-enzyme systems (isozymes) representing 22 human chromosomes. A concordance between BEV expression and the presence of human chromosome six was observed (97% synteny in 160 analyzed clones) defining a new genetic locus (Bevi) required for productive BEV infection. Southern blot analyses of integrated proviral DNA in hybrid clones showed that (1) cells segregating human chromosome six also segregated the integrated BEV provirus and (2) BEV is integrated at random molecular sites in human DNA. Thus Bevi is either a preferred complex locus for integration of BEV in human DNA or, alternatively, is a regulatory gene providing functions critical for maintaining the integrated BEV provirus.